ArticleOncotarget2014
The KLK5 protease suppresses breast cancer by repressing the mevalonate pathway.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 37 citations in OpenAlex.
- Sterol regulatory element‑binding proteins: Master regulators of lipid metabolic reprogramming in cancer and emerging therapeutic targets (Review).Oncology reports · 2026Review
- ADAMTS-8 and kallikrein-related peptidases 10 and 5 proteases also have a tumor suppression role.World journal of clinical oncology · 2025Review
- BC-predict: mining of signal biomarkers and production of models for early-stage breast cancer subtyping and prognosis.Frontiers in bioinformatics · 2025Article
- Bioinformatics analysis of human kallikrein 5 (Cancer innovation · 2023Article
- Kallikrein-Related Peptidase 12 (KLK12) in Breast Cancer as a Favorable Prognostic Marker.International journal of molecular sciences · 2023Article
- Ovarian Cancer Radiosensitivity: What Have We Understood So Far?Life (Basel, Switzerland) · 2022Review
- Activity-Based Probes for Proteases Pave the Way to Theranostic Applications.Pharmaceutics · 2022Review
- Remodelling of the tumour microenvironment by the kallikrein-related peptidases.Nature reviews. Cancer · 2022Review
- SPINKs in Tumors: Potential Therapeutic Targets.Frontiers in oncology · 2022Review
- Transcript-targeted analysis reveals isoform alterations and double-hop fusions in breast cancer.Communications biology · 2021Article
- Kallikreins emerge as new regulators of viral infections.Cellular and molecular life sciences : CMLS · 2021Review
- Article
- PPARα-Selective Antagonist GW6471 Inhibits Cell Growth in Breast Cancer Stem Cells Inducing Energy Imbalance and Metabolic Stress.Biomedicines · 2021Article
- Inclusion of endophenotypes in a standard GWAS facilitate a detailed mechanistic understanding of genetic elements that control blood lipid levels.Scientific reports · 2020Article
- Advanced high-grade serous ovarian cancer: inverse association of KLK13 and KLK14 mRNA levels in tumor tissue and patients' prognosis.Journal of cancer research and clinical oncology · 2018Article
- Article
- SPINK6 Promotes Metastasis of Nasopharyngeal Carcinoma via Binding and Activation of Epithelial Growth Factor Receptor.Cancer research · 2017Article
- Altered Mitochondrial Signalling and Metabolism in Cancer.Frontiers in oncology · 2017Review
- Article
- Assessment of kallikrein-related peptidase 5 (KLK5) protein expression in tumor tissue of advanced ovarian cancer patients by immunohistochemistry and ELISA: correlation with clinical outcome.American journal of cancer research · 2016Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Kallikrein-related peptidase 5 (KLK5) displays aberrant expression in cancer. However, any functional association is missing. Here, we show that reconstitution of KLK5 expression in non-expressing MDA-MB-231 breast cancer cells suppresses malignancy in vitro and in vivo dose-dependently. Reactivation of KLK5 suppressed key EMT genes. Unexpectedly, we identified altered expression of genes encoding enzymes of the mevalonate pathway typical of those observed upon cholesterol starvation. Consistently, we found that SREBF1, the master regulator of the mevalonate pathway was induced. KLK5 re-expression leads to reduced cellular cholesterol and fatty acid synthesis and enhanced uptake of LDL-cholesterol. Suppression of the mevalonate pathway in KLK5 transfectants was further shown by reduced synthesis of isoprenoids. Indeed, we found diminished levels of active RhoA, a signaling oncoprotein that requires prenylation for activation. We propose that reduced RhoA activation plays a dominant role in suppression of malignancy by KLK5, since geranylgeranyl pyrophosphate restored active RhoA in KLK5-reverted cells resulting in increased malignancy. For the first time, we suggest that a protease may suppress breast cancer by modulating the mevalonate pathway.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.